In 1984, J. David Erickson and his research team published the
results of a study titled "Vietnam Veterans' Risks for Fathering
Babies with Birth Defects" that indicated that Vietnam veterans were
at increased risk of fathering infants with serious congenital
malformations, or birth defects[6]. Researchers at the Centers for
Disease Control (CDC) in Atlanta, Georgia, conducted the study to
address the issue. Though the study's results were inconclusive, the study was
one of the first to document a possible association between Vietnam
War service and spina bifida[7], a lower back birth defect in which the
spinal cord does not form properly. Later research established the
links between Agent Orange exposure and various birth defects[6] and
led the US Department of Veterans Affairs to offer disability
compensation for Vietnam veterans and their families who were
affected by Agent Orange exposure.

During the Vietnam War, from 1961 to 1970, the US military
sprayed approximately nineteen million gallons of herbicides over
Vietnam as part of a defoliation and crop destruction campaign
called Operation Ranch Hand. Protests from scientists and citizens
over the possible health and ecological consequences of Operation
Ranch Hand led to a government-mandated study in 1965 on the
possible toxicity of the herbicides, and one herbicide in
particular, Agent Orange. The study showed that Agent Orange
contained a synthetic dioxin compound,
2,3,7,8-tetrachlorodibenzodioxin (TCDD), which caused fetal
malformations and stillbirths in rodents exposed to TCDD while in
utero. Following the study's results, the US military
discontinued Operation Ranch Hand in 1971.

Before the war ended in 1975, civilians in Vietnam began to
report an increased occurrence of birth abnormalities and
stillbirths in areas that had been targeted by Agent Orange. Vietnam
veterans from New Zealand, Australia, and the US made similar
reports, and they reported a higher occurrence of specific cancers
and skin diseases. In 1978, a group of US veterans further
highlighted those consequences when they filed a lawsuit against the chemical
manufacturers of the herbicides used in the Vietnam War.

The Centers for Disease Control subsequently began a study in
1982 to determine if Vietnam veterans were more likely to father
infants with birth defects[6]. The researchers who conducted the CDC
study were J. David Erickson, Joseph Mulinare, Philip W. McClain,
Terry G. Fitch, Levy M. James, Anne B. McClearn, and Myron J. Adams,
Jr. Erickson was the Chief of the Birth Defects and Genetic Diseases
Branch of the National Center for Environmental Health in Atlanta,
Georgia, and the other authors were medical epidemiologists at the
CDC. The team summarized the results in the Journal of the
American Medical Association[8] publication, and the CDC also
released a comprehensive report on the study.

"Vietnam Veterans' Risks for Fathering Babies with Birth
Defects" is a 10-page paper with a short introduction and 3 main
sections: "Methods," "Results," and "Comment." The "Methods"
section is further divided into 3 sections: "Selection of Cases and
Controls," "Study Data," and "Analytic Approach." According to
Erickson and his colleagues, to study the link between Agent Orange
and the occurrence of birth defects[6], they measured the amount of
Agent Orange to which the veterans had been exposed. The authors
state that the best way to measure herbicide exposure was to
question individual Vietnam veterans about their war experience and
then to study the health outcomes of their children. Although women
were also exposed to Agent Orange in Vietnam, the study looked at
predominantly men to study how paternal exposure to chemicals might
be related to birth defects[6] in children.

Erickson and his colleagues begin the introduction of the paper
by explaining that the purpose of the study is to address Vietnam
veteran concerns and to provide a brief overview of the use of Agent
Orange in the Vietnam War. The authors state that certain chemicals
are known to affect pregnant women, but that the link between
paternal exposure to chemicals and birth defects[6] is largely unknown.
In the final part of the introduction, the authors reassert that
their primary goal was not to focus on the link between Agent Orange
and birth defects[6], but to determine if Vietnam veterans in general
were at increased risk of fathering infants with birth defects[6].

The authors next begin the first main section, "Methods,"
starting with the subsection, "Selection of Cases and Controls."
Erickson and his colleagues explain how they selected the case
group, which consisted of infants with birth defects[6], and the
control group, which consisted of infants without birth defects[6]. The
researchers identified affected infants who were born from 1968
through 1980 through the Metropolitan Atlanta Congenital Defects
Program, a program that attempted to identify all individuals born
with birth defects[6] diagnosed during the first year of life.
Furthermore, researchers chose for the case group only infants with
serious structural congenital malformations, or birth defects[6], such
as a substantial handicap, premature death, or a defect that
required surgery or extensive medical care. The researchers included
7,133 infants with birth defects[6] in the case group.

Erickson and his colleagues selected the control group infants
from the 323,421 infants who were born in the Atlanta area during
the same twelve-year period. With the aid of the State of Georgia
Vital Records Unit, they chose infants that approximately matched
the case group by race, year of birth, and hospital of birth,
finally including 4,246 infants in the control group.

Following the formation of the case group and the control group,
the researchers interviewed the infants' families over the course of
a year, from 1982 to 1983. They explain the details of the
interviews in the second subsection, "Study Data." The authors note
that they located the parents by using information available the
infants' birth certificates or medical records. The authors of the
study also note that locating the parents was difficult due to the
lack of accurate information. Upon locating the parents, the
researchers asked them to participate in a study designed to learn
about the causes of birth defects[6]. Due to the controversy
surrounding the Vietnam War and Agent Orange, the researchers did
not initially mention either during the interviews to further avoid
potential bias that might lead Vietnam veterans to over-report
adverse health outcomes.

After a family agreed to participate, two interviewers
questioned each mother and father over the phone. The first
interviewer asked about the parent's reproductive history. The
second interviewer asked about potential causes of birth defects[6],
like exposure to certain chemicals in occupations, and the parents'
history of chronic diseases and drug use. Because reproductive
histories included descriptions of the infant's health, there was no
way to conceal the case or control status of the infant in question
from the first interviewer, which could potentially bias the
interviewers conducting of the interview. To minimize interviewer
bias, the second interviewer did not know the case or control-group
status of the infant. If both mother and father agreed to complete
interviews, then a total of four interviewers contacted one family,
two for each parent. Of the 7,133 case-group infants, 4,929 mothers
and 3,977 fathers completed interviews. Of the 4,246 control-group
infants, 3,029 mothers and 2,426 fathers completed interviews. The
authors note that a major reason that parents did not participate
was because they were not able to locate them.

The researchers also instructed the interviewers to obtain a
history of paternal military service during interviews with either
parent. Erickson and his colleagues defined veterans as fathers who
had served in the US military at any time, and Vietnam veterans as
fathers who had served in Vietnam before the conception[9] of their
children. Interviewers asked fathers who identified themselves as
Vietnam veterans if they believed they had been exposed to Agent
Orange. Their answers were then referred to the Army Agent Orange
Task Force, a panel of service specialists from the US Department of
Defense, to assign each veteran an Exposure Opportunity Index (EOI)
score.

The EOI score was a graded score from one to five, with one
meaning limited opportunities for exposure to Agent Orange, and five
meaning high opportunities for exposure. A total of two EOI
evaluations were assigned to each Vietnam veteran in the study, one
according to their self-reports and one according to the veteran's
military records. The second EOI score was determined by specialists
who reviewed each Vietnam veteran's occupation, location, and time
of service in Vietnam and compared them to military records of
herbicide application. According to Erickson and his colleagues, it
was difficult to verify the accuracy of the veterans' self-reports
or the accuracy of the EOI scoring. Herbicide records that were
available at the time were not made for health studies but for
military records, meaning that the information was not intended to
be used to estimate herbicide exposure and subsequent health
effects. They conclude the second subsection by stating that despite
those potential inaccuracies, they felt that the EOI scores were the
only possible way to measure Agent Orange exposure at that time.

In the last subsection of the "Methods" section, titled
"Analytic Approach," Erickson and his colleagues explain how they
used the EOI scores. They first categorized all the birth defects[6]
that affected the case group infants into 96 categories. They then
determined if any of the categories of birth defects[6] was linked to a
specific cohort, either Vietnam veterans in general or Vietnam
veterans with a particular set of EOI scores. The groups included
categories of broadly labeled defects, such as total nervous system
defects and total respiratory tract defects, and specific defects,
such as spina bifida[7] and hydrocephalus[10], which are birth defects[6]
involving the brain, spine, and spinal cord. One group included all
of the birth defects[6] affecting the case group infants, aptly named
"All Case Babies." Infants with more than one defect were included
in each relevant group.

Within each of the 96 groups, the researchers sought to answer
four questions relating to all US veterans, Vietnam veterans, the
veterans' EOI scores, and the veterans' self-reported Agent Orange
experiences. First, they determined whether the risk of fathering
infants with birth defects[6] was greater for all veterans (not just
Vietnam veterans) than for non-veterans. The authors say that they
chose that question because they thought that Vietnam veterans might
be at increased risk of fathering infants with birth defects[6]
relative to other veterans, but at decreased risk relative to
nonveterans.

The second question, about Vietnam veteran status asked whether
Vietnam veterans were at greater risk than all other men for
fathering infants with birth defects[6].

The third question evaluated whether the veterans' risk of
fathering infants with birth defects[6] was related to their EOI
scores. The assessment was conducted twice, once with the EOI score
obtained from military records and once with the EOI score derived
from the veterans' self-reports.

Lastly, the researchers asked if there was a correlation between
Vietnam veterans who reported that they had been exposed to Agent
Orange, regardless of their EOI scores, and the health outcomes of
their infant children. Regarding the last question, the authors
considered the possibility that veterans might be biased when
answering questions about Agent Orange. Specifically, men who had
fathered children with birth defects[6] might already believe that
Agent Orange caused those birth defects[6], which may affect their
answers regarding their exposure to Agent Orange and other
herbicides. To account for this possibility, researchers evaluated
the fourth question by comparing data on one type of defect with
data on all other types of defects, assuming that a parent with a
biased answer would only affect one category of birth defects[6], and
not all categories.

The researchers evaluated each of the questions three times for
each of the 96 categories. Using statistical methods, they
determined each veteran's risk of fathering infants with birth
defects. If Vietnam veterans had twice the risk as other men, their
relative risk was 2.0. If the veterans' risk was half that of other
men, their relative risk was 0.5. If Vietnam veterans were at
greater risk, then there would be a higher percentage of Vietnam
veterans among fathers of infants with birth defects[6], and a smaller
percentage of Vietnam veterans in the control group.

The authors conclude the "Methods" section by summarizing three
additional issues related to Vietnam military service that they
evaluated in the study. They first determined if fathers of infants
with particular birth defects[6] were more frequently Vietnam veterans.
Secondly, researchers assessed whether Vietnam veterans were at an
increased risk of fathering multiple children with birth defects[6].
Thirdly, they asked if Vietnam veteran fathers had contracted
malaria in Vietnam, a tropical disease transmitted by mosquitoes
that affected over 40,000 US soldiers during the war, and if
veterans had taken anti-malarial medicine. They asked about malaria
because malaria or anti-malarial medicine might have been linked to
birth defects[6].

In the second main section of the paper, titled "Results," the
authors report the results of the interviews, their four questions,
and the three supplementary issues they examined. Of the eligible
families in both groups, 69.9% (7,958) of mothers and 56.3% (6,403)
of fathers completed interviews. Approximately, an additional 1% of
mothers and fathers completed partial interviews to the point that
the interviewers obtained paternal military history. For the first
question, which compared all veterans with nonveterans,
approximately 38% of fathers in the case group were veterans,
compared to approximately 39% of fathers in the control group. The
relative risk was 0.94, meaning that veterans in general did not
have increased risk for fathering infants with birth defects[6].
Because Vietnam veterans and non-Vietnam veterans were not at
increased risk, the researchers evaluated the remaining three
questions by comparing Vietnam veterans' risks to those of
nonveterans and veterans combined.

For the second question, Erickson and his colleagues report that
when all types of defects were combined, 9.2% of case group fathers
had served in Vietnam, compared to 9.5% of fathers in the control
group. Because the proportions were similar, and the estimated
relative risk was 0.97, the researchers concluded that the risk of
Vietnam veterans for fathering infants with birth defects[6] was not
significantly different from that of other fathers. They found
similar results in the remaining 95 groups of birth defects[6].

Lastly, the results of the third and fourth questions show that
Vietnam veterans who had been assigned higher Agent Orange EOI
scores or veterans who believed they had been exposed to Agent
Orange did not have significantly higher risk of fathering infants
with all birth defects[6] combined. The results of all four tests
across all 96 groups are displayed in a table that covered two pages
of the journal article.

The four questions produced similar results in most defect
groups. However, the authors of the study note several statistically
significant findings. Vietnam veterans with higher EOI scores had a
higher estimated risk for fathering infants with spina bifida[7], a
defect characterized by an improperly formed spinal cord, which can
cause partial or complete lower body paralysis. Veterans with a
higher EOI score also had higher estimated risks for fathering
infants with cleft lip with or without cleft palate, a birth defect
marked by an improperly formed lip or mouth. Those with higher EOI
scores also had higher risks of fathering infants with defects
related to tumor growth, including benign tumors and cysts found
under the skin. The researchers report that in the category "Total
Sex Organ Defects," fathers of those infants were more likely to
have reported that they contracted malaria while they were in
Vietnam, pointing to an apparent association between paternal
contraction of malaria and sex organ birth defects[6] in the offspring.

In the final "Comment" section of the article, Erickson and his
colleagues discuss the conclusions that they draw from the study.
They consider their findings which did not suggest that Vietnam
veterans were at greater risk than other men for fathering infants
with all types of serious structural birth defects[6] combined to be
the most important conclusion from their study. The authors note
that structural birth defects[6], when combined, affect roughly two to
three percent of stillborn and live-born babies, and that
statistically, two to three percent of infants born to returning
Vietnam veterans were born with serious defects. Therefore, one
could expect that a certain proportion of fathers in the case group
would be Vietnam veterans, and that the presence of birth defects[6]
did not necessarily imply that there were external factors other
than the usual rate that birth defects[6] occur. The authors next say
that the study does not prove if the cause of birth defects[6] was a
factor associated with service in Vietnam. They argue that their
first conclusion regarding Vietnam veterans in general was based on
relatively strong evidence, despite not addressing the actual cause
of the birth defects[6] in the study.

Based on the third and fourth questions, the authors also
concluded that Vietnam veterans' risk for fathering infants with
birth defects[6] did not increase with higher EOI scores or with higher
self-reported Agent Orange exposure. However, they stated that they
considered that second conclusion regarding the association with
Agent Orange to be based on considerably weaker evidence than the
primary conclusion about Vietnam veterans in general, due to the
potential inaccuracy of the EOI scores. They note that to further
study the association between increased risk of fathering infants
with birth defects[6] and Agent Orange exposure, researchers need to
consider select groups of Vietnam veterans or specific types of
defects. Despite the uncertain validity of the EOI scores, Erickson
and his colleagues cite their use of the veterans' self-reports as a
strength of the study.

The authors then address the statistically significant results
of the study, prefacing their summary by saying that irregular
results should be expected of any study with multiple hypotheses.
Specifically, they highlight that a statistically significant result
was not necessarily correlated with an increased or different risk
of fathering an infant with a specific birth defect. Regarding the
finding that veterans with higher EOI scores seemed more likely to
father infants with spina bifida[7], the authors attribute the
association with spina bifida[7] to chance. This was because veterans
with higher EOI scores were not found to have higher estimated risk
for fathering infants with anencephalus, a related defect of spina
bifida. The authors make the same attributions to chance occurred
with congenital neoplasms and the orofacial defects that include
cleft lip and cleft palate, due to statistical methods that pointed
to an unknown factor that affected the study.

The authors contextualize their results by summarizing the
results of related studies. At the time, there was only one other
study published on the association of birth defects[6] to Vietnam
service, conducted by researchers at the Commonwealth Institute of
Health at the University of Sydney, Australia. Titled "Case-Control
Study of Congenital Anomalies and Vietnam Service," the authors of
that study concluded that there was no increased risk of all types
of structural birth defects[6] combined among men who served in Vietnam
in the Australian Army. Other studies had been conducted on the
health effects of dioxins in non-military settings, like in
herbicide factories, but no adverse human reproductive effects had
been conclusively linked. And while the link had been solidified
between maternal exposure to drugs and subsequent reproductive
issues, Erickson and his colleagues note that the contribution of
paternal exposures to birth defects[6] had not been extensively
investigated.

In the last paragraph of the paper, the authors state that only
a limited number of studies had been published that focused on human
populations with well-documented exposure to herbicides and dioxins.
Due to the small scale of those studies, Erickson and his colleagues
claim that the inconclusive findings might reflect the weaknesses of
their study rather than a true lack of association. They reiterate
their belief that the estimates of Agent Orange exposure were likely
inaccurate, and therefore, their secondary conclusion regarding
Agent Orange associated risks for Vietnam veterans was also weak.
Erickson and his colleagues conclude the paper by stating that if
Agent Orange exposure was indeed linked to increased risk, then the
risk was either small, limited to select group of veterans, or
limited to specific types of defects.

When the paper was published in the Journal of the American
Medical Association in August of 1984, it was accompanied by an
editorial by Bruce Dan, senior editor of the Journal of the
American Medical Association[8]. In the editorial, Dan included a
brief overview of the use of herbicides in Vietnam, the toxicology
of Agent Orange and the contaminant TCDD, and the reported health
problems of veterans who had fought in Vietnam. He explained how
congenital malformations could be related to a man or woman's
exposure to chemicals. Dan argued that it was important to
investigate the link between Vietnam service and the rate of birth
defects because other factors aside from chemical exposure such as
stress, poor nutrition, and alcohol or drug abuse could increase the
incidence of birth defects[6]. After summarizing Erickson and
colleagues' paper, Dan concluded that it was unlikely that serious
birth defects[6] of Vietnam veterans' children were related to the
fathers' Vietnam experience.

Nearly a year later, on 2 August 1985, the Journal of the
American Medical Association[8] published a "To the Editor" letter
by Theodore Sterling and Anthony Arundel, two researchers at Simon
Fraser University in British Columbia, Canada. The letter, which
shared the same title as Erickson's paper, stated that there was a
difference between studying birth defects[6] among children of Vietnam
veterans, and studying birth defects[6] among children of Vietnam
veterans exposed to Agent Orange. Sterling and Arundel noted that
the Australian study and CDC study focused on the Vietnam link more
than the Agent Orange link. The authors also noted that the CDC's
findings of higher than expected rates of cleft palate and spina
bifida should not be dismissed as chance phenomena. They considered
the results significant because of other studies which had found
higher rates of cleft palate, spina bifida[7], and other birth defects[6]
related to improper neural tube[11] disclosure, after exposure or
possible exposure to 2,4,5-trichlorophenoxyacetic acid, one of the
main components of Agent Orange. Sterling and Arundel expressed
concern with Dan's editorial, which they said suggested that there
was no basis for a link between Agent Orange and birth defects[6]. They
concluded that the possible relationship between Agent Orange
exposure and birth defects[6] warranted further research, either by
studying exposed US Vietnam veterans, or studying exposed and
unexposed people in Vietnam.

The CDC study by Erickson and colleagues was the first US report
to assess the association between Vietnam military service and
serious congenital anomalies. In the late 1980s, the CDC conducted a
larger study in conjunction with the Veterans Administration called
the Vietnam Experience Study. The third part of that study focused
on the reproductive outcomes and child health of Vietnam veterans,
during which interview data also revealed higher numbers of
cerebrospinal malformations (like spina bifida[7]) in the children of
Vietnam veterans. However, the Vietnam Experience Study authors
concluded that there were no significant differences in the
occurrence of birth defects[6] between children of Vietnam and
non-Vietnam veterans, and that their findings were consistent with
previous epidemiologic studies, including the one by Erickson and
his colleagues.

In the early 1990s, US Congress enacted Public Law 102-4, more
commonly called the Agent Orange Act of 1991, which directed the US
National Academy of Sciences[12] to publish reports every two years that
reviewed and evaluated newly published scientific literature
regarding the effects of dioxin exposure, in particular pertaining
to Vietnam veterans and their families' health outcomes. In the 1996
report by the National Academy of Sciences[12] Institute of Medicine
committee, the authors acknowledged a link between Agent Orange
exposure and the occurrence of spina bifida[7] in children. The
conclusion led the US Veterans Administration to provide disability
benefits to Vietnam veterans' children with spina bifida[7], marking
the first time that the Veterans Administration provided
compensation to veterans' family members.

Sterling, Theodore D., and A. Arundel. "Letters to the Editor:
Vietnam Veterans Risk for Fathering Children with Birth Defects."
Journal of the American Medical Association[8] 254 (1985): 609.

U.S. Department of Health, Education and Welfare, Public Health
Service, Center for Disease Control. Health Status of Vietnam
Veterans: The Centers for Disease Control Vietnam Experience
Study. Washington, D.C.: US Department of Health and Human
Services, 1989.

In 1984, J. David Erickson and his research team published the results of a study titled 'Vietnam Veterans' Risks for Fathering Babies with Birth Defects' that indicated that Vietnam veterans were at increased risk of fathering infants with serious congenital malformations, or birth defects. Researchers at the Centers for Disease Control (CDC) in Atlanta, Georgia, conducted the study to address Though the study's results were inconclusive, the study was one of the first to document a possible association between Vietnam War service and spina bifida, a lower back birth defect in which the spinal cord does not form properly. Later research established the links between Agent Orange exposure and various birth defects and led the US Department of Veterans Affairs to offer disability compensation for Vietnam veterans and their families who were affected by Agent Orange exposure.